Relevant prior art to the subject of the present invention may be found in the following publications:
1) U.S. Pat. No. 3,172,816. PA1 2) EP-82-214501. PA1 3) EP-A3-215313. PA1 4) Benita, S., Friedman, D. and Weinstock, M. (1986), International Journal of Pharmaceutics, 30: 47-55. PA1 5) Singh, M. and Ravin, J. (1986), J. Parenteral Sci. Technol. 40: 34-41. PA1 6) Von Dardel, 0., Mebius, C. and Mossberg, T. (1976), Acta Anaesth. Scand. 20:221-224.
The utilization of pharmaceutical compositions in the form of emulsions of drugs having low aqueous solubility is well known in the art. However, as a rule such compositions are of low stability due to fast phase separation between the oil and the water phases, which is further enhanced by the hydrophobic drugs for which the emulsions serve as carriers.
Many hydrophobic drugs are important for various medical treatments, but since they are relatively unstable and insoluble in water their most useful form of administration is by way of an oil-in-water emulsion-type composition, in which the drug is dissolved in the oil phase. This is in effect the only practical way by which such hydrophobic drugs can be administered intravenously.
In accordance with the prior art stability of compositions of this type was unsatisfactory since as stated above, the hydrophobic drugs destabilize such compositions. Another drawback of prior art emulsion type compositions is that they tend to lose their stability when they are sterilized in an autoclave which is the most efficient and least costly way of sterilizing such compositions. During autoclaving the oily droplets of the emulsion coalesce and consequently creaming and/or phase separation occurs. This therefore necessitated hitherto the use of other forms of sterilization such as filtration.
It is the object of the present invention to provide compositions of the oil-in-water type emulsions containing hydrophobic drugs, which are stable over prolonged storage and furthermore where the drug is heat resistant, are capable of being sterilized by autoclaving without a change in their properties or loss of their stability. It is a further object of the present invention to provide such compositions for parenteral, oral, occular and topical administration of said drug.